AstraZeneca and Ironwood Pharmaceuticals, Inc., an entrepreneurial pharmaceutical company dedicated to the art and science of great drug-making, have entered into an agreement to co-develop and co-commercialise Ironwood’s linaclotide in China. Linaclotide is the first and only guanylate cyclase-C (GC-C) agonist approved by the US Food and Drug Administration, in August, for irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC).
In May, Ironwood filed a clinical trial application with the State Food and Drug Administration in China for a phase III clinical trial to assess the efficacy and safety of linaclotide in adult patients suffering from irritable bowel syndrome with constipation (IBS-C). IBS-C, which is characterised by symptoms of abdominal pain and constipation, is a chronic and prevalent functional gastrointestinal disorder in China and there are currently few treatment options for this condition.
“China is one of the fastest growing prescription medicines markets in the world and linaclotide represents a valuable opportunity to meet the needs of local patients by providing an innovative new treatment option,” said Mark Mallon, regional vice-president for Asia Pacific and president, AstraZeneca China. “We are pleased to be collaborating with Ironwood for linaclotide in China, which capitalises on our leadership in the gastrointestinal sector in the emerging markets.”
Peter Hecht, Ironwood’s chief executive officer, said: “As we continue to advance our efforts to make linaclotide available to patients around the world, we are excited about this opportunity to collaborate in China with AstraZeneca, one of the world’s most successful companies in gastrointestinal medicine.”
AstraZeneca and Ironwood are jointly responsible for strategic oversight of the development and commercialisation of linaclotide in China. AstraZeneca will have primary responsibility for the local operational execution.
Under the terms of the collaboration, AstraZeneca will make an upfront payment of $25 million to Ironwood and will share the net profits and losses associated with linaclotide in China, with AstraZeneca carrying 55 per cent of each until a certain specified milestone is achieved, moving to a 50/50 split thereafter. Ironwood will also be eligible for $125 million in additional commercial milestone payments contingent on the achievement of certain sales targets.
In addition, the companies also announced today their agreement that Ironwood’s sales force of approximately 160 experienced clinical sales specialists will promote AstraZeneca’s Nexium (esomeprazole magnesium) in the US. Nexium is a leading prescription drug currently approved to treat the symptoms of gastroesophageal reflux disease (GERD). This agreement will augment AstraZeneca’s existing interactions with gastroenterologists and primary care physicians on behalf of Nexium and the patients who need it. It will also provide Ironwood with an opportunity to increase its presence with the key gastrointestinal physicians in the US.
“A large percentage of adult patients who have IBS-C or who have CIC, may also suffer from GERD,” said Thomas McCourt, chief commercial officer, senior vice-president, marketing and sales, Ironwood Pharmaceuticals. “This agreement provides our experienced clinical sales specialists with the opportunity to bring two different and effective therapies to physicians for managing their patients who have these prevalent and troublesome gastrointestinal disorders.”
Linaclotide is a guanylate cyclase-C (GC-C) agonist that is provided as an oral capsule intended for once-daily administration.
It binds to guanylate cyclase C locally in the intestine, with no measurable blood plasma concentrations, resulting in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP). Elevations in intracellular cGMP are believed to stimulate secretion of intestinal fluid and accelerate gastrointestinal transit resulting in increased frequency of bowel movements. Elevations in extracellular cGMP are believed to decrease activity of pain-sensing nerves, which is thought to be responsible for a reduction in intestinal pain, according to non-clinical models.